TP53 mutation status divides myelodysplastic syndromes with complex karyotypes into distinct prognostic subgroups. | Aplastic Anemia & MDS International Foundation

TP53 mutation status divides myelodysplastic syndromes with complex karyotypes into distinct prognostic subgroups.

Journal Title: 
Leukemia
Primary Author: 
Haase D
Author(s): 
Haase D, Stevenson KE, Neuberg D, Maciejewski JP, Nazha A, Sekeres MA, Ebert BL, Garcia-Manero G, Haferlach C, Haferlach T, Kern W, Ogawa S, Nagata Y, Yoshida K, Graubert TA, Walter MJ, List AF, Komrokji RS, Padron E, Sallman D, Papaemmanuil E, Campbell P
Original Publication Date: 
Friday, January 11, 2019
Risk stratification is critical in the care of patients with myelodysplastic syndromes (MDS). Approximately 10% have a complex karyotype (CK), defined as more than two cytogenetic abnormalities, which is a highly adverse prognostic marker. However, CK-MDS can carry a wide range of chromosomal abnormalities and somatic mutations. To refine risk stratification of CK-MDS patients, we examined data from 359 CK-MDS patients shared by the International Working Group for MDS. Mutations were underrepresented with the exception of TP53 mutations, identified in 55% of patients. TP53 mutated patients had even fewer co-mutated genes but were enriched for the del(5q) chromosomal abnormality (p < 0.005), monosomal karyotype (p < 0.001), and high complexity, defined as more than 4 cytogenetic abnormalities (p < 0.001). Monosomal karyotype, high complexity, and TP53 mutation were individually associated with shorter overall survival, but monosomal status was not significant in a multivariable model. Multivariable survival modeling identified severe anemia (hemoglobin < 8.0 g/dL), NRAS mutation, SF3B1 mutation, TP53 mutation, elevated blast percentage (>10%), abnormal 3q, abnormal 9, and monosomy 7 as having the greatest survival risk. The poor risk associated with CK-MDS is driven by its association with prognostically adverse TP53 mutations and can be refined by considering clinical and karyotype features.
Bone Marrow Diseases: